Selective organ cooling apparatus and method

ABSTRACT

An endovascular heat transfer device which can have a smooth exterior surface, or a surface with ridges and grooves. The device can have a plurality of elongated, articulated segments, with each having such a surface. A flexible joint connects adjacent elongated, articulated segments. The flexible joints can be bellows or flexible tubes. An inner lumen is disposed within the heat transfer segments. The inner lumen is capable of transporting a pressurized working fluid to a distal end of the heat transfer element.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This is a continuation patent application of co-pending U.S.patent application Ser. No. 10/161,107, filed on May 30, 2002, andentitled “Selective Organ Cooling Apparatus and Method”; which is acontinuation patent application of co-pending U.S. patent applicationSer. No. 09/607,799, filed on Jun. 30, 2000, and entitled “SelectiveOrgan Cooling Apparatus and Method”; which is a continuation-in-partpatent application of co-pending U.S. patent application Ser. No.09/570,075, filed on May 12, 2000, and entitled “Selective Organ CoolingApparatus and Method”; a continuation-in-part patent application of U.S.patent application Ser. No. 09/215,041, filed on Dec. 16, 1998, andentitled “Articulation Device for Selective Organ Cooling Apparatus”,now U.S. Pat. No. 6,254,626; a continuation-in-part patent applicationof U.S. patent application Ser. No. 09/103,342, filed on Jun. 23, 1998,and entitled “Selective Organ Cooling Catheter and Method of Using theSame”, now U.S. Pat. No. 6,096,068; a continuation-in-part patentapplication of U.S. patent application Ser. No. 09/052,545, filed onMar. 31, 1998, and entitled “Circulating Fluid Hypothermia Method andApparatus”, now U.S. Pat. No. 6,231,595; and a continuation-in-partpatent application of U.S. patent application Ser. No. 09/047,012, filedon Mar. 24, 1998, and entitled “Selective Organ Hypothermia Method andApparatus”, now U.S. Pat. No. 5,957,963; and a continuation-in-partpatent application of U.S. patent application Ser. No. 09/012,287, filedon Jan. 23, 1998, and entitled “Selective Organ Hypothermia Method andApparatus”, now U.S. Pat. No. 6,051,019. The disclosures of these parentapplications are hereby incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not Applicable

BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates generally to the modification andcontrol of the temperature of a selected body organ. More particularly,the invention relates to a method and intravascular apparatus forcontrolling organ temperature.

[0005] 2. Background Art

[0006] Organs in the human body, such as the brain, kidney and heart,are maintained at a constant temperature of approximately 37° C.Hypothermia can be clinically defined as a core body temperature of 35°C. or less. Hypothermia is sometimes characterized further according toits severity. A body core temperature in the range of 33° C. to 35° C.is described as mild hypothermia. A body temperature of 28°0 C. to 32°C. is described as moderate hypothermia. A body core temperature in therange of 24° C. to 28° C. is described as severe hypothermia.

[0007] Hypothermia is uniquely effective in reducing brain injury causedby a variety of neurological insults and may eventually play animportant role in emergency brain resuscitation. Experimental evidencehas demonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

[0008] Cerebral hypothermia has traditionally been accomplished throughwhole body cooling to create a condition of total body hypothermia inthe range of 20° C. to 30°0 C. However, the use of total bodyhypothermia risks certain deleterious systematic vascular effects. Forexample, total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

[0009] Catheters have been developed which are inserted into thebloodstream of the patient in order to induce total body hypothermia.For example, U.S. Pat. No. 3,425,419 to Dato describes a method andapparatus of lowering and raising the temperature of the human body.Dato induces moderate hypothermia in a patient using a metalliccatheter. The metallic catheter has an inner passageway through which afluid, such as water, can be circulated. The catheter is insertedthrough the femoral vein and then through the inferior vena cava as faras the right atrium and the superior vena cava. The Dato catheter has anelongated cylindrical shape and is constructed from stainless steel. Byway of example, Dato suggests the use of a catheter approximately 70 cmin length and approximately 6 mm in diameter. However, use of the Datodevice implicates the negative effects of total body hypothermiadescribed above.

[0010] Due to the problems associated with total body hypothermia,attempts have been made to provide more selective cooling. For example,cooling helmets or head gear have been used in an attempt to cool onlythe head rather than the patient's entire body. However, such methodsrely on conductive heat transfer through the skull and into the brain.One drawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

[0011] Selected organ hypothermia has been accomplished usingextracorporeal perfusion, as detailed by Arthur E. Schwartz, M.D. etal., in Isolated Cerebral Hypothermia by Single Carotid Artery Perfusionof Extracorporeally Cooled Blood in Baboons, which appeared in Vol. 39,No. 3, NEUROSURGERY 577 (September, 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

[0012] Selective organ hypothermia has also been attempted by perfusionof a cold solution such as saline or perfluorocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

[0013] Therefore, a practical method and apparatus which modifies andcontrols the temperature of a selected organ satisfies a long-felt need.

BRIEF SUMMARY OF THE INVENTION

[0014] The apparatus of the present invention can, by way of exampleonly, include a heat transfer element which comprises first and secondelongated, articulated segments, each segment can have either aturbulence-inducing or mixing-inducing exterior surface or a smoothexterior surface. A flexible joint can connect the first and secondelongated segments. An inner coaxial lumen may be disposed within thefirst and second elongated segments and is capable of transporting apressurized working fluid to a distal end of the first elongatedsegment. In addition, the first and second elongated segments may have aturbulence-inducing or mixing-inducing interior surface for inducingturbulence or mixing within the pressurized working fluid. Theturbulence-inducing or mixing-inducing exterior surface may be adaptedto induce turbulence or mixing within a free stream of blood flow whenplaced within an artery. The turbulence-inducing exterior surface may beadapted to induce a turbulence intensity greater than 0.05 within a freestream blood flow. In one embodiment, the flexible joint comprises abellows section which also allows for axial compression of the heattransfer element. In another embodiment, the flexible joint comprises astraight, flexible tube as disclosed in U.S. patent application Ser. No.09/215,041, filed on Dec. 16, 1998, and entitled “Articulation Devicefor Selective Organ Cooling Apparatus”, the disclosure of which isentirely incorporated herein by reference.

[0015] In one embodiment, the turbulence-inducing or mixing-inducingexterior surfaces of the heat transfer element comprise one or morealternating ridges and grooves. The ridges and grooves can be alignedlongitudinally along the heat transfer element, or they can be arrangedhelically around the heat transfer element. Where straight ridges andgrooves are used, adjacent segments can have their ridges angularlyoffset from each other, to increase turbulence or mixing. Similarly,where helical ridges are used, adjacent segments of the heat transferelement can be oppositely spiraled, to increase turbulence or mixing.For instance, the first elongated heat transfer segment may comprise oneor more helical ridges having a counter-clockwise twist, while thesecond elongated heat transfer segment comprises one or more helicalridges having a clockwise twist. Alternatively, of course, the firstelongated heat transfer segment may comprise one or more clockwisehelical ridges, and the second elongated heat transfer segment maycomprise one or more counter-clockwise helical ridges. The first andsecond elongated, articulated segments may be formed from highlyconductive materials, such as a metal, or a polymer doped or loaded withparticles or filaments of a conductive material. Where the surface hassufficiently pronounced features such as ridges, the enhanced surfacearea alone may provide sufficient heat transfer, without a need forangular offsets, or opposite spirals, to induce turbulence or mixing.

[0016] In another embodiment, the turbulence-inducing or mixing-inducingexterior surface of the heat transfer element is adapted to induceturbulence or mixing throughout the duration of each pulse of apulsatile blood flow when placed within an artery. In still anotherembodiment, the turbulence-inducing or mixing-inducing exterior surfaceof the heat transfer element is adapted to induce turbulence or mixingduring at least 20% of the period of each cardiac cycle when placedwithin an artery.

[0017] In yet another embodiment, the exterior surface of the heattransfer element may be an entirely smooth surface, such as a rightcircular cylinder. The segments of the heat transfer element can have asmooth exterior surface, where the surface area is large enough toprovide sufficient heat transfer. Here again, the articulated segmentsmay be formed from highly conductive materials, such as a metal, or apolymer doped or loaded with particles or filaments of a conductivematerial.

[0018] The heat transfer device may also have a coaxial supply catheterwith an inner catheter lumen coupled to the inner coaxial lumen withinthe first and second elongated heat transfer segments. A working fluidsupply configured to dispense the pressurized working fluid may becoupled to the inner catheter lumen. The working fluid supply may beconfigured to produce the pressurized working fluid at a temperature ofabout 0° C. and at a pressure below about 5 atmospheres of pressure.

[0019] In yet another alternative embodiment, the heat transfer devicemay have three or more elongated, articulated, heat transfer segmentshaving a turbulence-inducing, mixing-inducing, or smooth exteriorsurface, with additional flexible joints connecting the additionalelongated heat transfer segments. In one such embodiment, by way ofexample, the first and third elongated heat transfer segments maycomprise clockwise helical ridges, and the second elongated heattransfer segment may comprise one or more counter-clockwise helicalridges. Alternatively, of course, the first and third elongated heattransfer segments may comprise counter-clockwise helical ridges, and thesecond elongated heat transfer segment may comprise one or moreclockwise helical ridges. As still another alternative, in the use oflongitudinal ridges, the second elongated heat transfer segment may havelongitudinal ridges offset by a radial angle from the longitudinalridges on the first segment, and the third heat transfer segment mayhave longitudinal ridges offset by a radial angle from the longitudinalridges on the second segment. As yet another alternative, of course,each elongated heat transfer segment can be a smooth right circularcylinder. Further, a mixture of these types of elongated heat transfersegments can be used on a heat transfer device.

[0020] The turbulence-inducing, mixing-inducing, or smooth exteriorsurface of the heat transfer element may optionally include a surfacecoating or treatment to inhibit clot formation. One variation of theheat transfer element comprises a stent coupled to a distal end of thefirst elongated heat transfer segment.

[0021] The present invention also envisions a method of treating thebrain which comprises the steps of inserting a flexible, conductive heattransfer element into a carotid artery from a distal location, andcirculating a working fluid through the flexible, conductive heattransfer element in order to selectively modify the temperature of thebrain without significantly modifying the temperature of the entirebody. The flexible, conductive heat transfer element preferably absorbsmore than about 25, 50 or 75 Watts of heat.

[0022] The method may also comprise the step of inducing turbulence ormixing within the free stream blood flow within the carotid artery. Inone embodiment, the method includes the step of inducing bloodturbulence with a turbulence intensity greater than about 0.05 withinthe carotid artery. In another embodiment, the method includes the stepof inducing blood turbulence or mixing throughout the duration of theperiod of the cardiac cycle within the carotid artery. In yet anotherembodiment, the method comprises the step of inducing blood turbulenceor mixing throughout the period of the cardiac cycle within the carotidartery or during greater than about 20% of the period of the cardiaccycle within the carotid artery. The step of circulating may comprisethe step of inducing turbulent flow or mixing of the working fluidthrough the flexible, conductive heat transfer element. The pressure ofthe working fluid may be maintained below about 5 atmospheres ofpressure.

[0023] The present invention also envisions a method for selectivelycooling an organ in the body of a patient which comprises the steps ofintroducing a catheter, with a heat transfer element, into a bloodvessel supplying the organ, the catheter having a diameter of about 4 mmor less, inducing free stream turbulence or mixing in blood flowing overthe heat transfer element, and cooling the heat transfer element toremove heat from the blood to cool the organ without substantiallycooling the entire body. In one embodiment, the cooling step removes atleast about 75 Watts of heat from the blood. In another embodiment, thecooling step removes at least about 100 Watts of heat from the blood.The organ being cooled may be the human brain.

[0024] The step of inducing free stream turbulence may induce aturbulence intensity greater than about 0.05 within the blood vessel.The step of inducing free stream turbulence may induce turbulencethroughout the duration of each pulse of blood flow. The step ofinducing free stream turbulence may induce turbulence for at least about20% of the duration of each pulse of blood flow.

[0025] In one embodiment, the catheter has a flexible metal, or dopedpolymer, tip and the cooling step occurs at the tip. The tip may havesmooth, turbulence-inducing, or mixing-inducing elongated heat transfersegments separated by bellows sections. The turbulence-inducing ormixing-inducing segments may comprise longitudinal or helical ridgeswhich are configured to have a depth which is greater than a thicknessof a boundary layer of blood which develops within the blood vessel. Inanother embodiment, the catheter has a tip at which the cooling stepoccurs and the tip has turbulence-inducing or mixing-inducing elongatedheat transfer segments that alternately spiral bias the surroundingblood flow in clockwise and counterclockwise directions.

[0026] The cooling step may comprise the step of circulating a workingfluid in through an inner lumen in the catheter and out through anouter, coaxial lumen. In one embodiment, the working fluid remains aliquid throughout the cycle. The working fluid may be aqueous.

[0027] The present invention also envisions a cooling cathetercomprising a catheter shaft having first and second lumens therein. Thecooling catheter also comprises a cooling tip adapted to transfer heatto or from a working fluid circulated in through the first lumen and outthrough the second lumen, and either a smooth exterior surface orturbulence-inducing or mixing-inducing structures on the cooling tipcapable of inducing free stream turbulence or mixing when the tip isinserted into a blood vessel. The turbulence-inducing structures mayinduce a turbulence intensity of at least about 0.05. The cooling tipmay be adapted to induce turbulence or mixing within the working fluid.The catheter is capable of removing at least about 25 Watts of heat froman organ when inserted into a vessel supplying that organ, while coolingthe tip with a working fluid that remains a liquid in the catheter.Alternatively, the catheter is capable of removing at least about 50 or75 Watts of heat from an organ when inserted into a vessel supplyingthat organ, while cooling the tip with an aqueous working fluid. In oneembodiment, in use, the tip has a diameter of about 4 mm or less.Optionally, the turbulence-inducing or mixing-inducing surfaces on theheat transfer segments comprise longitudinal or helical ridges whichhave a depth sufficient to disrupt the free stream blood flow in theblood vessel. Alternatively, the turbulence-inducing or mixing-inducingsurfaces may comprise staggered protrusions from the outer surfaces ofthe heat transfer segments, which have a height sufficient to disruptthe free stream flow of blood within the blood vessel.

[0028] In another embodiment, a cooling catheter may comprise a cathetershaft having first and second lumens therein, a cooling tip adapted totransfer heat to or from a working fluid circulated in through the firstlumen and out through the second lumen, and either a smooth exteriorsurface or turbulence-inducing or mixing-inducing structures on thecooling tip capable of inducing turbulence or mixing when the tip isinserted into a blood vessel. Alternatively, a cooling catheter maycomprise a catheter shaft having first and second lumens therein, acooling tip adapted to transfer heat to or from a working fluidcirculated in through the first lumen and out through the second lumen,and structures on the cooling tip capable of inducing free streamturbulence or mixing when the tip is inserted into a blood vessel. Inanother embodiment, a cooling catheter may comprise a catheter shafthaving first and second lumens therein, a cooling tip adapted totransfer heat to or from a working fluid circulated in through the firstlumen and out through the second lumen, and turbulence-inducingstructures on the cooling tip capable of inducing turbulence with anintensity greater than about 0.05 when the tip is inserted into a bloodvessel.

[0029] The novel features of this invention, as well as the inventionitself, will be best understood from the attached drawings, taken alongwith the following description, in which similar reference charactersrefer to similar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0030]FIG. 1 is a graph illustrating the velocity of steady stateturbulent flow as a function of time;

[0031]FIG. 2A is a graph showing the velocity of the blood flow withinan artery as a function of time;

[0032]FIG. 2B is a graph illustrating the velocity of steady stateturbulent flow under pulsatile conditions as a function of time, similarto arterial blood flow;

[0033]FIG. 2C is an elevation view of a turbulence inducing heattransfer element within an artery;

[0034]FIG. 3A is a velocity profile diagram showing a typical steadystate Poiseuillean flow driven by a constant pressure gradient;

[0035]FIG. 3B is a velocity profile diagram showing blood flow velocitywithin an artery, averaged over the duration of the cardiac pulse;

[0036]FIG. 3C is a velocity profile diagram showing blood flow velocitywithin an artery, averaged over the duration of the cardiac pulse, afterinsertion of a smooth heat transfer element within the artery;

[0037]FIG. 4 is an elevation view of one embodiment of a heat transferelement according to the invention, with alternating helices;

[0038]FIG. 5 is longitudinal section view of the heat transfer elementof FIG. 4;

[0039]FIG. 6 is a transverse section view of the heat transfer elementof FIG. 4;

[0040]FIG. 7 is a perspective view of the heat transfer element of FIG.4 in use within a blood vessel;

[0041]FIG. 8 is a cut-away perspective view of a second embodiment of aheat transfer element according to the invention, with protrusions onthe surface;

[0042]FIG. 9 is a transverse section view of the heat transfer elementof FIG. 8;

[0043]FIG. 10 is a schematic representation of the invention being usedin one embodiment to cool the brain of a patient;

[0044]FIG. 11 is a perspective view of a third embodiment of a heattransfer element according to the invention, with aligned longitudinalridges on adjacent segments;

[0045]FIG. 12 is a perspective view of a fourth embodiment of a heattransfer element according to the invention, with offset longitudinalridges on adjacent segments; and

[0046]FIG. 13 is a transverse section view of the heat transfer elementof FIG. 11 or FIG. 12.

DETAILED DESCRIPTION OF THE INVENTION

[0047] In order to intravascularly regulate the temperature of aselected organ, a heat transfer element may be placed in the feedingartery of the organ to absorb or deliver the heat from or to the bloodflowing into the organ. The transfer of heat may cause either a coolingor a heating of the selected organ. The heat transfer element must besmall enough to fit within the feeding artery while still allowing asufficient blood flow to reach the organ in order to avoid ischemicorgan damage. A heat transfer element which selectively cools an organshould be capable of providing the necessary heat transfer rate toproduce the desired cooling or heating effect within the organ. Byplacing the heat transfer element within the feeding artery of an organ,the temperature of an organ can be controlled without significantlyaffecting the remaining parts of the body. These points can beillustrated by using brain cooling as an example.

[0048] The common carotid artery supplies blood to the head and brain.The internal carotid artery branches off of the common carotid todirectly supply blood to the brain. To selectively cool the brain, theheat transfer element is placed into the common carotid artery, or boththe common carotid artery and the internal carotid artery. The internaldiameter of the common carotid artery ranges from 6 to 8 mm and thelength ranges from 80 to 120 mm. Thus, the heat transfer elementresiding in one of these arteries cannot be much larger than 4 mm indiameter in order to avoid occluding the vessel.

[0049] It is important that the heat transfer element be flexible inorder to be placed within the small feeding artery of an organ. Feedingarteries, like the carotid artery, branch off the aorta at variouslevels. Subsidiary arteries continue to branch off the initial branches.For example, the internal carotid artery is a small diameter artery thatbranches off of the common carotid artery near the angle of the jaw.Because the heat transfer element is typically inserted into aperipheral artery, such as the femoral artery, and accesses the feedingartery by initially passing though a series of one or more of thesebranches, the flexibility of the heat transfer element is an importantcharacteristic of the heat transfer element. Further, the heat transferelement is ideally constructed from a highly thermally conductivematerial such as metal, or a metal-doped polymer, in order to facilitateheat transfer. The use of a highly thermally conductive materialincreases the heat transfer rate for a given temperature differentialbetween the coolant within the heat transfer element and the blood. Thisfacilitates the use of a higher temperature coolant within the heattransfer element, allowing safer coolants, such as water, to be used.Highly thermally conductive materials, such as metals, tend to be rigid.Therefore, the design of the heat transfer element should facilitateflexibility in an inherently inflexible material. Alternatively, theheat transfer element can be constructed of a flexible polymer doped orloaded with particles or filaments of a conductive material, such as ametal.

[0050] In order to obtain the benefits of hypothermia described above,it is desirable to reduce the temperature of the blood flowing to thebrain to between 30° C. and 32° C. Given that a typical brain has ablood flow rate through each carotid artery (right and left) ofapproximately 250-375 cubic centimeters per minute, the heat transferelement should absorb 75-175 Watts of heat when placed in one of thecarotid arteries, in order to induce the desired cooling effect. Itshould be noted that smaller organs may have less blood flow in thesupply artery and may require less heat transfer, such as 25 Watts.

[0051] When a heat transfer element is inserted coaxially into anartery, the primary mechanism of heat transfer between the surface ofthe heat transfer element and the blood is forced convection. Convectionrelies upon the movement of fluid to transfer heat. Forced convectionresults when an external force causes motion within the fluid. In thecase of arterial flow, the beating heart causes the motion of the bloodaround the heat transfer element.

[0052] The magnitude of the heat transfer rate is proportional to thesurface area of the heat transfer element, the temperature differential,and the heat transfer coefficient of the heat transfer element.

[0053] As noted above, the receiving artery into which the heat transferelement is placed has a limited diameter and length. Thus, surface areaof the heat transfer element must be limited, to avoid significantobstruction of the artery, and to allow the heat transfer element toeasily pass through the vascular system. For placement within theinternal and common carotid artery, the cross sectional diameter of theheat transfer element is limited to about 4 mm, and its length islimited to approximately 10 cm.

[0054] The temperature differential can be increased by decreasing thesurface temperature of the heat transfer element. However, the minimumallowable surface temperature is limited by the characteristics ofblood. Blood freezes at approximately 0° C. When the blood approachesfreezing, ice emboli may form in the blood which may lodge downstream,causing serious ischemic injury. Furthermore, reducing the temperatureof the blood also increases its viscosity, which results in a smalldecrease in the value of the convection heat transfer coefficient. Inaddition, increased viscosity of the blood may result in an increase inthe pressure drop within the artery, thus, compromising the flow ofblood to the brain. Given the above constraints, it is advantageous tolimit the minimum allowable surface temperature of the heat transferelement to approximately 5° C. This results in a maximum temperaturedifferential between the blood stream and the heat transfer element ofapproximately 32° C.

[0055] The mechanisms by which the value of the convection heat transfercoefficient may be increased are complex. A heat transfer element with asmooth exterior surface may be able to provide the desired amount ofheat transfer. However, it is well known that the convection heattransfer coefficient increases with the level of turbulent kineticenergy in the fluid flow. Thus, if flow past a smooth heat transferelement will not transfer sufficient heat, it is advantageous to haveturbulent or otherwise mixed blood flow in contact with the heattransfer element.

[0056]FIG. 1 is a graph illustrating steady state turbulent flow. Thevertical axis is the velocity of the flow. The horizontal axisrepresents time. The average velocity of the turbulent flow is shown bya line 100. The actual instantaneous velocity of the flow is shown by acurve 102.

[0057] Under constant pressure conditions, steady flows in pipes arecharacterized as a balance between viscous stresses and the constantpressure gradient. Such flows are called Poiseuillean. FIG. 3A is avelocity profile diagram showing a typical steady state Poiseuilleanflow driven by a constant pressure gradient. The velocity of the fluidacross the pipe is shown in FIG. 3A by the parabolic curve andcorresponding velocity vectors. The velocity of the fluid in contactwith the wall of the pipe is zero. The boundary layer is the region ofthe flow in contact with the pipe surface in which viscous stresses aredominant. In steady state Poiseuillean flow, the boundary layer developsuntil it includes the whole pipe, i.e., the boundary layer thickness inFIG. 3A is one half of the diameter of the pipe.

[0058] Under conditions of Poiseuillean flow, the Reynolds number, theratio of inertial forces to viscous forces, can be used to characterizethe level of turbulent kinetic energy existing in the flow. ForPoiseuillean flows, Reynolds numbers must be greater than about 2300 tocause a transition from laminar to turbulent flow. Further, when theReynolds number is greater than about 2000, the boundary layer isreceptive to “tripping”. Tripping is a process by which a smallperturbation in the boundary layer can create turbulent conditions. Thereceptivity of a boundary layer to “tripping” is proportional to theReynolds number and is nearly zero for Reynolds numbers less than 2000.

[0059] In contrast with the steady Poiseuillean flow, the blood flow inarteries is induced by the beating heart and is therefore pulsatile.FIG. 2A is a graph showing the velocity of the blood flow within anartery as a function of time. The beating heart provides pulsatile flowwith an approximate period of 0.5 to 1 second. This is known as theperiod of the cardiac cycle. The horizontal axis in FIG. 2A representstime in seconds and the vertical axis represents the average velocity ofblood in centimeters per second. Although very high velocities arereached at the peak of the pulse, the high velocity occurs for only asmall portion of the cycle. In fact, the velocity of the blood reacheszero in the carotid artery at the end of a pulse and temporarilyreverses.

[0060] Because of the relatively short duration of the cardiac pulse,the blood flow in the arteries does not develop into the classicPoiseuillean flow. FIG. 3B is a velocity profile diagram showing bloodflow velocity within an artery averaged over the cardiac pulse. Themajority of the flow within the artery has the same velocity. Theboundary layer where the flow velocity decays from the free stream valueto zero is very thin, typically ⅙ to {fraction (1/20)} of the diameterof the artery, as opposed to one half of the diameter of the artery inthe Poiseuillean flow condition.

[0061] As noted above, if the flow in the artery were steady rather thanpulsatile, the transition from laminar to turbulent flow would occurwhen the value of the Reynolds number exceeds about 2,000. However, inthe pulsatile arterial flow, the value of the Reynolds number variesduring the cardiac cycle, just as the flow velocity varies. In pulsatileflows, due to the enhanced stability associated with the acceleration ofthe free stream flow, the critical value of the Reynolds number at whichthe unstable modes of motion grow into turbulence is found to be muchhigher, perhaps as high as 9,000.

[0062] The blood flow in the arteries of interest remains laminar overmore than 80% of the cardiac cycle. Referring again to FIG. 2A, theblood flow is turbulent from approximately time t₁ until time t₂ duringa small portion of the descending systolic flow, which is less than 20%of the period of the cardiac cycle. If a heat transfer element is placedinside the artery, heat transfer will be facilitated during this shortinterval. However, to transfer the necessary heat to cool the brain,turbulent kinetic energy should be produced in the blood stream andsustained throughout the entire period of the cardiac cycle.

[0063] A thin boundary layer has been shown to form during the cardiaccycle. This boundary layer will form over the surface of a smooth heattransfer element. FIG. 3C is a velocity profile diagram showing bloodflow velocity within an artery, averaged over the cardiac pulse, afterinsertion of a smooth heat transfer element within the artery. In FIG.3C, the diameter of the heat transfer element is about one half of thediameter of the artery. Boundary layers develop adjacent to the heattransfer element as well as next to the walls of the artery. Each ofthese boundary layers has approximately the same thickness as theboundary layer which would have developed at the wall of the artery inthe absence of the heat transfer element. The free stream flow region isdeveloped in an annular ring around the heat transfer element. Bloodflow past such a smooth heat transfer element may transfer sufficientheat to accomplish the desired temperature control.

[0064] One way to increase the heat transfer rate is to create aturbulent boundary layer on the heat transfer element surface. However,turbulence in the very thin boundary layer will not produce sufficientkinetic energy to produce the necessary heat transfer rate. Therefore,to induce sufficient turbulent kinetic energy to increase the heattransfer rate sufficiently to cool the brain, a stirring mechanism,which abruptly changes the direction of velocity vectors, should beutilized. This can create high levels of turbulence intensity in thefree stream, thereby sufficiently increasing the heat transfer rate.

[0065] This turbulence intensity should ideally be sustained for asignificant portion of the cardiac cycle. Further, turbulent kineticenergy should ideally be created throughout the free stream and not justin the boundary layer. FIG. 2B is a graph illustrating the velocity ofcontinually turbulent flow under pulsatile conditions as a function oftime, which would result in optimal heat transfer in arterial bloodflow. Turbulent velocity fluctuations are seen throughout the cycle asopposed to the short interval of fluctuations seen in FIG. 2A betweentime t₁ and time t₂. These velocity fluctuations are found within thefree stream. The turbulence intensity shown in FIG. 2B is at least 0.05.In other words, the instantaneous velocity fluctuations deviate from themean velocity by at least 5%. Although, ideally, turbulence or mixing iscreated throughout the entire period of the cardiac cycle, the benefitsof turbulence are also obtained if the turbulence or mixing is sustainedfor only 75%, 50% or even as low as 30% or 20% of the cardiac cycle.

[0066] To create the desired level of turbulence intensity or mixing inthe blood free stream during the whole cardiac cycle, one embodiment ofthe invention uses a modular design. This design creates helical bloodflow and produces a high level of mixing in the free stream.

[0067] For a swirling flow in a tube in which the azimuthal velocity ofthe fluid vanishes toward the stationary outer boundary, anynon-vanishing azimuthal velocity in the interior of the flow will resultin an instability in which the inner fluid is spontaneously exchangedwith fluid near the wall, analogous to Taylor cells in the purelyazimuthal flow between a rotating inner cylinder and stationary outercylinder. This instability results from the lack of any force inopposition to the centripetal acceleration of the fluid particles movingalong helical paths, the pressure in the tube being a function only oflongitudinal position. In one embodiment the device of the presentinvention imparts an azimuthal velocity to the interior of a developedpipe flow, with the net result being a continuous exchange of fluidbetween the core and perimeter of the flow as it moves longitudinallydown the pipe. This fluid exchange enhances the transport of heat,effectively increasing the convective heat transfer coefficient overthat which would have obtained in undisturbed pipe flow. This bulkexchange of fluid is not necessarily turbulent, although turbulence ispossible if the induced azimuthal velocity is sufficiently high.

[0068]FIG. 2C is a perspective view of such a turbulence inducing ormixing-inducing heat transfer element within an artery. In thisembodiment, turbulence or mixing is further enhanced by periodicallyforcing abrupt changes in the direction of the helical blood flow.Turbulent or mixed flow would be found at point 114, in the free streamarea. The abrupt changes in flow direction are achieved through the useof a series of two or more heat transfer segments, each comprised of oneor more helical ridges. Ideally, the segments will be close enoughtogether to prevent re-laminarization of the flow in between segments.

[0069] The use of periodic abrupt changes in the helical direction ofthe blood flow in order to induce strong free stream turbulence ormixing may be illustrated with reference to a common clothes washingmachine. The rotor of a washing machine spins initially in one directioncausing laminar flow. When the rotor abruptly reverses direction,significant turbulent kinetic energy is created within the entire washbasin as the changing currents cause random turbulent mixing motionwithin the clothes-water slurry.

[0070]FIG. 4 is an elevation view of one embodiment of a heat transferelement 14 according to the present invention. The heat transfer element14 is comprised of a series of elongated, articulated segments ormodules 20, 22, 24. Three such segments are shown in this embodiment,but two or more such segments could be used without departing from thespirit of the invention. As seen in FIG. 4, a first elongated heattransfer segment 20 is located at the proximal end of the heat transferelement 14. A turbulence-inducing or mixing-inducing exterior surface ofthe segment 20 comprises four parallel helical ridges 28 with fourparallel helical grooves 26 therebetween. One, two, three, or moreparallel helical ridges 28 could also be used without departing from thespirit of the present invention. In this embodiment, the helical ridges28 and the helical grooves 26 of the heat transfer segment 20 have aleft hand twist referred to herein as a counter-clockwise spiral orhelical rotation, as they proceed toward the distal end of the heattransfer segment 20.

[0071] The first heat transfer segment 20 is coupled to a secondelongated heat transfer segment 22 by a first flexible section such as abellows section 25, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as shown in FIG. 3C, butflexible. The second heat transfer segment 22 comprises one or morehelical ridges 32 with one or more helical grooves 30 therebetween. Theridges 32 and grooves 30 have a right hand, or clockwise, twist as theyproceed toward the distal end of the heat transfer segment 22. Thesecond heat transfer segment 22 is coupled to a third elongated heattransfer segment 24 by a second flexible section such as a bellowssection 27 or a flexible tube. The third heat transfer segment 24comprises one or more helical ridges 36 with one or more helical grooves34 therebetween. The helical ridge 36 and the helical groove 34 have aleft hand, or counter-clockwise, twist as they proceed toward the distalend of the heat transfer segment 24. Thus, successive heat transfersegments 20, 22, 24 of the heat transfer element 14 alternate betweenhaving clockwise and counterclockwise helical twists. The actual left orright hand twist of any particular segment is immaterial, as long asadjacent segments have opposite helical twist.

[0072] In addition, the rounded contours of the ridges 28, 32, 36 alsoallow the heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element according to the present inventionmay be comprised of two, three, or more heat transfer segments.

[0073] The bellows sections 25, 27 are formed from seamless andnonporous materials, such as metal, and therefore are impermeable togas, which can be particularly important, depending on the type ofworking fluid which is cycled through the heat transfer element 14. Thestructure of the bellows sections 25, 27 allows them to bend, extend andcompress, which increases the flexibility of the heat transfer element14 so that it is more readily able to navigate through blood vessels.The bellows sections 25, 27 also provide for axial compression of theheat transfer element 14, which can limit the trauma when the distal endof the heat transfer element 14 abuts a blood vessel wall. The bellowssections 25, 27 are also able to tolerate cryogenic temperatures withouta loss of performance, facilitating use of the heat transfer element inlow temperature ablation of tissue.

[0074] As an alternative to a heat transfer element 14 made entirely ofa metal or a metal-doped polymer, the exterior surfaces of the heattransfer element 14 can be made from metal, and this metal may comprisevery high thermal conductivity materials such as nickel, therebyfacilitating heat transfer. Alternatively, other metals such asstainless steel, titanium, aluminum, silver, copper and the like, can beused, with or without an appropriate coating or treatment to enhancebiocompatibility or inhibit clot formation. Suitable biocompatiblecoatings include, e.g., gold, platinum or polymer paralyene. The heattransfer element 14 may be manufactured by plating a thin layer of metalon a mandrel that has the appropriate pattern. In this way, the heattransfer element 14 may be manufactured inexpensively in largequantities, which is an important feature in a disposable medicaldevice.

[0075] Because the heat transfer element 14 may dwell within the bloodvessel for extended periods of time, such as 24-48 hours or even longer,it may be desirable to treat the surfaces of the heat transfer element14 to avoid clot formation. In particular, one may wish to treat thebellows sections 25, 27 because stagnation of the blood flow may occurin the convolutions, thus allowing clots to form and cling to thesurface to form a thrombus. One means by which to prevent thrombusformation is to bind an antithrombogenic agent to the surface of theheat transfer element 14. For example, heparin is known to inhibit clotformation and is also known to be useful as a biocoating. Alternatively,the surfaces of the heat transfer element 14 may be bombarded with ionssuch as nitrogen. Bombardment with nitrogen can harden and smooth thesurface and, thus prevent adherence of clotting factors to the surface.

[0076]FIG. 5 is a longitudinal sectional view of the heat transferelement 14 of an embodiment of the invention, taken along line 5-5 inFIG. 4. Some interior contours are omitted for purposes of clarity. Aninner tube 42 creates an inner coaxial lumen 42 and an outer coaxiallumen 46 within the heat transfer element 14. Once the heat transferelement 14 is in place in the blood vessel, a working fluid such assaline or other aqueous solution may be circulated through the heattransfer element 14. Fluid flows up a supply catheter into the innercoaxial lumen 40. At the distal end of the heat transfer element 14, theworking fluid exits the inner coaxial lumen 40 and enters the outerlumen 46. As the working fluid flows through the outer lumen 46, heat istransferred from the working fluid to the exterior surface 37 of theheat transfer element 14. Because the heat transfer element 14 isconstructed from a high conductivity material, the temperature of itsexterior surface 37 may reach very close to the temperature of theworking fluid. The tube 42 may be formed as an insulating divider tothermally separate the inner lumen 40 from the outer lumen 46. Forexample, insulation may be achieved by creating longitudinal airchannels in the wall of the insulating tube 42. Alternatively, theinsulating tube 42 may be constructed of a non-thermally conductivematerial like polytetrafluoroethylene or some other polymer.

[0077] It is important to note that the same mechanisms that govern theheat transfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants such as freon undergonucleate boiling and create turbulence through a different mechanism.Saline is a safe coolant because it is non-toxic, and leakage of salinedoes not result in a gas embolism, which could occur with the use ofboiling refrigerants. Since turbulence or mixing in the coolant isenhanced by the shape of the interior surface 38 of the heat transferelement 14, the coolant can be delivered to the heat transfer element 14at a warmer temperature and still achieve the necessary heat transferrate. Further, as the working fluid passes through a bellows sectioninto a heat transfer segment, the bellows can create a “jet effect” intothe adjacent heat transfer segment, thereby enhancing interior mixing.

[0078] This has a number of beneficial implications in the need forinsulation along the catheter shaft length. Due to the decreased needfor insulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

[0079]FIG. 6 is a transverse sectional view of the heat transfer element14 of the invention, taken at a location denoted by the line 6-6 in FIG.4. FIG. 6 illustrates a five lobed embodiment, whereas FIG. 4illustrates a four-lobed embodiment. As mentioned earlier, any number oflobes might be used. In FIG. 6, the coaxial construction of the heattransfer element 14 is clearly shown. The inner coaxial lumen 40 isdefined by the insulating coaxial tube 42. The outer lumen 46 is definedby the exterior surface of the insulating coaxial tube 42 and theinterior surface 38 of the heat transfer element 14. In addition, thehelical ridges 32 and helical grooves 30 may be seen in FIG. 6. Ifdesired, the depth of the grooves, d, can be greater than the boundarylayer thickness which would have developed if a cylindrical heattransfer element were introduced. For example, in a heat transferelement 14 with a 4 mm outer diameter, the depth of the invaginations,d, may be approximately equal to 1 mm if designed for use in the carotidartery. Although FIG. 6 shows four ridges and four grooves, the numberof ridges and grooves may vary. Thus, heat transfer elements with 1, 2,3, 4, 5, 6, 7, 8 or more ridges are specifically contemplated.

[0080]FIG. 7 is a perspective view of a heat transfer element 14 in usewithin a blood vessel, showing only one helical lobe per segment forpurposes of clarity. Beginning from the proximal end of the heattransfer element (not shown in FIG. 7), as the blood moves forwardduring the systolic pulse, the first helical heat transfer segment 20induces a counter-clockwise rotational inertia to the blood. As theblood reaches the second segment 22, the rotational direction of theinertia is reversed, causing turbulence or mixing within the blood.Further, as the blood reaches the third segment 24, the rotationaldirection of the inertia is again reversed. The sudden changes in flowdirection actively reorient and randomize the velocity vectors, thusensuring turbulence or mixing throughout the bloodstream. Duringturbulent or mixed flow, the velocity vectors of the blood become morerandom and, in some cases, become perpendicular to the axis of theartery. In addition, as the velocity of the blood within the arterydecreases and reverses direction during the cardiac cycle, additionalturbulence or mixing is induced and turbulent motion is sustainedthroughout the duration of each pulse through the same mechanismsdescribed above.

[0081] Thus, a large portion of the volume of warm blood in the vesselis actively brought in contact with the heat transfer element 14, whereit can be cooled by direct contact rather than being cooled largely byconduction through adjacent laminar layers of blood. In this embodiment,free stream turbulence or mixing is induced. Where a smooth heattransfer element is not sufficient, in order to create the desired levelof turbulence or mixing in the entire blood stream during the wholecardiac cycle, the heat transfer element 14 creates a turbulenceintensity greater than about 0.05. The turbulence intensity may begreater than 0.05, 0.06, 0.07 or up to 0.10 or 0.20 or greater.

[0082] Referring back to FIG. 4, the heat transfer element 14 has beendesigned to address all of the design criteria discussed above. First,the heat transfer element 14 is flexible and is made of a highlyconductive material. The flexibility is provided by a segmentaldistribution of flexible sections such as bellows sections 25, 27 orflexible tubes, which provide an articulating mechanism. Bellows have aknown convoluted design which provides flexibility. Second, the exteriorsurface area 37 has been increased through the use of helical ridges 28,32, 36 and helical grooves 26, 30, 34. The ridges also allow the heattransfer element 14 to maintain a relatively atraumatic profile, therebyminimizing the possibility of damage to the vessel wall. Third, the heattransfer element 14 has been designed to promote turbulent kineticenergy both internally and externally. The modular or segmental designallows the direction of the invaginations to be reversed betweensegments. The alternating helical rotations create an alternating flowthat results in mixing the blood in a manner analogous to the mixingaction created by the rotor of a washing machine that switchesdirections back and forth. This mixing action is intended to promotehigh level turbulent kinetic energy to enhance the heat transfer rate.The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

[0083]FIG. 8 is a cut-away perspective view of a second embodiment of aheat transfer element 50. An external surface 52 of the heat transferelement 50 is covered with a series of axially staggered protrusions 54.The staggered nature of the outer protrusions 54 is readily seen withreference to FIG. 9 which is a transverse cross-sectional view taken ata location denoted by the line 9-9 in FIG. 8. If desired, the height,d_(p), of the staggered outer protrusions 54 can be greater than thethickness of the boundary layer which would develop if a smooth heattransfer element had been introduced into the blood stream. As the bloodflows along the external surface 52, it collides with one of thestaggered protrusions 54 and a turbulent wake flow is created behind theprotrusion. As the blood divides and swirls along side of the firststaggered protrusion 54, its turbulent wake encounters another staggeredprotrusion 54 within its path preventing the re-lamination of the flowand creating yet more turbulence. In this way, the velocity vectors arerandomized and turbulence or mixing is created not only in the boundarylayer but throughout the free stream. As is the case with the preferredembodiment, this geometry also induces a turbulent or mixing effect onthe internal coolant flow.

[0084] A working fluid is circulated up through an inner coaxial lumen56 defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52, in order to induceturbulent or mixing flow of the working fluid. The inner protrusions canbe aligned with the outer protrusions 54, as shown in FIG. 9, or theycan be offset from the outer protrusions 54, as shown in FIG. 8.

[0085] The embodiment of FIGS. 8 and 9 may result in a Nusselt number(“Nu”) of about 1 to 50. The Nusselt number is the ratio of the heattransfer rate with fluid flow to the heat transfer rate in the absenceof fluid flow Nu=Q_(flow)/Q_(no/flow). The magnitude of the enhancementin heat transfer by fluid flow can be estimated by the Nusselt number.For convective heat transfer between blood and the surface of the heattransfer element, Nusselt numbers of 30 to 80 have been found to beappropriate for selective cooling applications of various organs in thehuman body. Nusselt numbers are generally dependent on several othernumbers: the Reynolds number, the Womersley number, and the Prandtlnumber. Enhancement of the heat transfer rate in embodiments of thepresent invention may be described by a Nusselt number of between 10 and50.

[0086]FIG. 10 is a schematic representation of the invention being usedto cool the brain of a patient. The selective organ hypothermiaapparatus shown in FIG. 10 includes a working fluid supply 10,preferably supplying a chilled liquid such as water, alcohol or ahalogenated hydrocarbon, a supply catheter 12 and the heat transferelement 14. The supply catheter 12 has a coaxial construction. An innercoaxial lumen within the supply catheter 12 receives coolant from theworking fluid supply 10. The coolant travels the length of the supplycatheter 12 to the heat transfer element 14 which serves as the coolingtip of the catheter. At the distal end of the heat transfer element 14,the coolant exits the insulated interior lumen and traverses the lengthof the heat transfer element 14 in order to decrease the temperature ofthe heat transfer element 14. The coolant then traverses an outer lumenof the supply catheter 12 so that it may be disposed of or recirculated.The supply catheter 12 is a flexible catheter having a diametersufficiently small to allow its distal end to be inserted percutaneouslyinto an accessible artery such as the femoral artery of a patient asshown in FIG. 10. The supply catheter 12 is sufficiently long to allowthe heat transfer element 14 at the distal end of the supply catheter 12to be passed through the vascular system of the patient and placed inthe internal carotid artery or other small artery. The method ofinserting the catheter into the patient and routing the heat transferelement 14 into a selected artery is well known in the art.

[0087] The working fluid supply 10 would preferably include a chillerand a pump. The pump can be a gear pump, a peristaltic pump, or someother type. A gear pump may be preferable, since the attainable pressurewith a gear pump may be higher, and the relationship of the volume flowrate to the pump speed may be more linear with a gear pump than withother pumps. Two types of gear pumps which would be suitable, amongothers, are radial spur gear pumps and helical tooth gear pumps. Ahelical tooth gear pump may provide higher pressure and more constantflow rate than a spur gear pump. The ability to achieve high pressuresmay be important, as the cooling fluid is required to pass through afairly narrow catheter at a certain, dependable, rate. For the samereason, the viscosity of the fluid, at low temperatures, should beappropriately low.

[0088] Although the working fluid supply 10 is shown as an exemplarycooling device, other devices and working fluids may be used. Forexample, in order to provide cooling, freon, perfluorocarbon, water, orsaline may be used, as well as other such coolants.

[0089] The heat transfer element can absorb or provide over 75 Watts ofheat to the blood stream and may absorb or provide as much as 100 Watts,150 Watts, 170 Watts or more. For example, a heat transfer element witha diameter of 4 mm and a length of approximately 10 cm using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2 atmospherescan absorb about 100 Watts of energy from the bloodstream. Smallergeometry heat transfer elements may be developed for use with smallerorgans which provide 60 Watts, 50 Watts, 25 Watts or less of heattransfer.

[0090]FIG. 11 is a perspective view of a third embodiment of a heattransfer element 70 according to the present invention. The heattransfer element 70 is comprised of a series of elongated, articulatedsegments or modules 72. A first elongated heat transfer segment 72 islocated at the proximal end of the heat transfer element 70. The segment72 may be a smooth right circular cylinder, as addressed in FIG. 3C, orit can incorporate a turbulence-inducing or mixing-inducing exteriorsurface. The turbulence-inducing or mixing-inducing exterior surfaceshown on the segment 72 in FIG. 11 comprises a plurality of parallellongitudinal ridges 74 with parallel longitudinal grooves 76therebetween. One, two, three, or more parallel longitudinal ridges 74could be used without departing from the spirit of the presentinvention. In the embodiment where they are used, the longitudinalridges 74 and the longitudinal grooves 76 of the heat transfer segment72 are aligned parallel with the axis of the first heat transfer segment72.

[0091] The first heat transfer segment 72 is coupled to a secondelongated heat transfer segment 72 by a first flexible section such as abellows section 78, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as addressed in FIG. 3C, butflexible. The second heat transfer segment 72 also comprises a pluralityof parallel longitudinal ridges 74 with parallel longitudinal grooves 76therebetween. The longitudinal ridges 74 and the longitudinal grooves 76of the second heat transfer segment 72 are aligned parallel with theaxis of the second heat transfer segment 72. The second heat transfersegment 72 is coupled to a third elongated heat transfer segment 72 by asecond flexible section such as a bellows section 78 or a flexible tube.The third heat transfer segment 72 also comprises a plurality ofparallel longitudinal ridges 74 with parallel longitudinal grooves 76therebetween. The longitudinal ridges 74 and the longitudinal grooves 76of the third heat transfer segment 72 are aligned parallel with the axisof the third heat transfer segment 72. Further, in this embodiment,adjacent heat transfer segments 72 of the heat transfer element 70 havetheir longitudinal ridges 74 aligned with each other, and theirlongitudinal grooves 76 aligned with each other.

[0092] In addition, the rounded contours of the ridges 74 also allow theheat transfer element 70 to maintain a relatively atraumatic profile,thereby minimizing the possibility of damage to the blood vessel wall. Aheat transfer element 70 according to the present invention may becomprised of two, three, or more heat transfer segments 72.

[0093] The bellows sections 78 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidwhich is cycled through the heat transfer element 70. The structure ofthe bellows sections 78 allows them to bend, extend and compress, whichincreases the flexibility of the heat transfer element 70 so that it ismore readily able to navigate through blood vessels. The bellowssections 78 also provide for axial compression of the heat transferelement 70, which can limit the trauma when the distal end of the heattransfer element 70 abuts a blood vessel wall. The bellows sections 78are also able to tolerate cryogenic temperatures without a loss ofperformance, facilitating use of the heat transfer element in lowtemperature ablation of tissue.

[0094]FIG. 12 is a perspective view of a fourth embodiment of a heattransfer element 80 according to the present invention. The heattransfer element 80 is comprised of a series of elongated, articulatedsegments or modules 82. A first elongated heat transfer segment 82 islocated at the proximal end of the heat transfer element 80. Aturbulence-inducing or mixing-inducing exterior surface of the segment82 comprises a plurality of parallel longitudinal ridges 84 withparallel longitudinal grooves 86 therebetween. One, two, three, or moreparallel longitudinal ridges 84 could be used without departing from thespirit of the present invention. In this embodiment, the longitudinalridges 84 and the longitudinal grooves 86 of the heat transfer segment82 are aligned parallel with the axis of the first heat transfer segment82.

[0095] The first heat transfer segment 82 is coupled to a secondelongated heat transfer segment 82 by a first flexible section such as abellows section 88, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as shown in FIG. 3C, butflexible. The second heat transfer segment 82 also comprises a pluralityof parallel longitudinal ridges 84 with parallel longitudinal grooves 86therebetween. The longitudinal ridges 84 and the longitudinal grooves 86of the second heat transfer segment 82 are aligned parallel with theaxis of the second heat transfer segment 82. The second heat transfersegment 82 is coupled to a third elongated heat transfer segment 82 by asecond flexible section such as a bellows section 88 or a flexible tube.The third heat transfer segment 82 also comprises a plurality ofparallel longitudinal ridges 84 with parallel longitudinal grooves 86therebetween. The longitudinal ridges 84 and the longitudinal grooves 86of the third heat transfer segment 82 are aligned parallel with the axisof the third heat transfer segment 82. Further, in this embodimentadjacent heat transfer segments 82 of the heat transfer element 80 havetheir longitudinal ridges 84 angularly offset from each other, and theirlongitudinal grooves 86 angularly offset from each other. Offsetting ofthe longitudinal ridges 84 and the longitudinal grooves 86 from eachother on adjacent segments 82 promotes turbulence or mixing in bloodflowing past the exterior of the heat transfer element 80.

[0096]FIG. 13 is a transverse section view of a heat transfer segment90, illustrative of segments 72, 82 of heat transfer elements 70, 80shown in FIG. 11 and FIG. 12. The coaxial construction of the heattransfer segment 90 is clearly shown. The inner coaxial lumen 92 isdefined by the insulating coaxial tube 93. The outer lumen 98 is definedby the exterior surface of the insulating coaxial tube 93 and theinterior surface 99 of the heat transfer segment 90. In addition,parallel longitudinal ridges 94 and parallel longitudinal grooves 96 maybe seen in FIG. 13. The longitudinal ridges 94 and the longitudinalgrooves 96 may have a relatively rectangular cross-section, as shown inFIG. 13, or they may be more triangular in cross-section, as shown inFIGS. 11 and 12. The longitudinal ridges 94 and the longitudinal grooves96 may be formed only on the exterior surface of the segment 90, with acylindrical interior surface 99. Alternatively, correspondinglongitudinal ridges and grooves may be formed on the interior surface 99as shown, to promote turbulence or mixing in the working fluid. AlthoughFIG. 13 shows six ridges and six grooves, the number of ridges andgrooves may vary. Where a smooth exterior surface is desired, the outertube of the heat transfer segment 90 could have smooth outer and innersurfaces, like the inner tube 93. Alternatively, the outer tube of theheat transfer segment 90 could have a smooth outer surface and a ridgedinner surface like the interior surface 99 shown in FIG. 13.

[0097] The practice of the invention is illustrated in the followingnon-limiting example.

Exemplary Procedure

[0098] 1. The patient is initially assessed, resuscitated, andstabilized.

[0099] 2. The procedure is carried out in an angiography suite orsurgical suite equipped with fluoroscopy.

[0100] 3. Because the catheter is placed into the common carotid artery,it is important to determine the presence of stenotic atheromatouslesions. A carotid duplex (doppler/ultrasound) scan can quickly andnon-invasively make this determinations. The ideal location forplacement of the catheter is in the left carotid so this may be scannedfirst. If disease is present, then the right carotid artery can beassessed. This test can be used to detect the presence of proximalcommon carotid lesions by observing the slope of the systolic upstrokeand the shape of the pulsation. Although these lesions are rare, theycould inhibit the placement of the catheter. Examination of the peakblood flow velocities in the internal carotid can determine the presenceof internal carotid artery lesions. Although the catheter is placedproximally to such lesions, the catheter may exacerbate the compromisedblood flow created by these lesions. Peak systolic velocities greaterthat 130 cm/sec and peak diastolic velocities >100 cm/sec in theinternal indicate the presence of at least 70% stenosis. Stenosis of 70%or more may warrant the placement of a stent to open up the internalartery diameter.

[0101] 4. The ultrasound can also be used to determine the vesseldiameter and the blood flow and the catheter with the appropriatelysized heat transfer element could be selected.

[0102] 5. After assessment of the arteries, the patients inguinal regionis sterilely prepped and infiltrated with lidocaine.

[0103] 6. The femoral artery is cannulated and a guide wire may beinserted to the desired carotid artery. Placement of the guide wire isconfirmed with fluoroscopy.

[0104] 7. An angiographic catheter can be fed over the wire and contrastmedia injected into the artery to further to assess the anatomy of thecarotid.

[0105] 8. Alternatively, the femoral artery is cannulated and a 10-12.5french (f) introducer sheath is placed.

[0106] 9. A guide catheter is placed into the desired common carotidartery. If a guiding catheter is placed, it can be used to delivercontrast media directly to further assess carotid anatomy.

[0107] 10. A 10 f-12 f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

[0108] 11. The cooling catheter is placed into the carotid artery viathe guiding catheter or over the guidewire. Placement is confirmed withfluoroscopy.

[0109] 12. Alternatively, the cooling catheter tip is shaped (angled orcurved approximately 45 degrees), and the cooling catheter shaft hassufficient pushability and torqueability to be placed in the carotidwithout the aid of a guide wire or guide catheter.

[0110] 13. The cooling catheter is connected to a pump circuit alsofilled with saline and free from air bubbles. The pump circuit has aheat exchange section that is immersed into a water bath and tubing thatis connected to a peristaltic pump. The water bath is chilled toapproximately 0° C.

[0111] 14. Cooling is initiated by starting the pump mechanism. Thesaline within the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

[0112] 15. It subsequently enters the cooling catheter where it isdelivered to the heat transfer element. The saline is warmed toapproximately 5-7° C. as it travels along the inner lumen of thecatheter shaft to the end of the heat transfer element.

[0113] 16. The saline then flows back through the heat transfer elementin contact with the inner metallic surface. The saline is further warmedin the heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood, cooling the blood to 30° to 32° C.

[0114] 17. The chilled blood then goes on to chill the brain. It isestimated that 15-30 minutes will be required to cool the brain to 30 to32° C.

[0115] 18. The warmed saline travels back down the outer lumen of thecatheter shaft and back to the chilled water bath where it is cooled to1° C.

[0116] 19. The pressure drops along the length of the circuit areestimated to be 2-3 atm.

[0117] 20. The cooling can be adjusted by increasing or decreasing theflow rate of the saline. Monitoring of the temperature drop of thesaline along the heat transfer element will allow the flow to beadjusted to maintain the desired cooling effect.

[0118] 21. The catheter is left in place to provide cooling for 12 to 24hours.

[0119] 22. If desired, warm saline can be circulated to promote warmingof the brain at the end of the therapeutic cooling period.

[0120] While the particular invention as herein shown and disclosed indetail is fully capable of obtaining the objects and providing theadvantages hereinbefore stated, it is to be understood that thisdisclosure is merely illustrative of the presently preferred embodimentsof the invention and that no limitations are intended other than asdescribed in the appended claims.

We claim:
 1. A heat transfer device for low temperature ablation oftissue, comprising: first and second elongated segments, one of saidfirst or second elongated segments providing a closed end of said heattransfer device; a bellows connecting said first and second elongatedsegments; and a tubular conduit disposed within and extendingsubstantially through said first and second elongated segments, saidconduit having an inner lumen for transporting a working fluid to adistal end of said one of said first or second elongated segmentsproviding a closed end of said heat transfer device.
 2. The devicerecited in claim 1, further comprising a smooth outer surface on atleast one of said first and second elongated segments.
 3. The devicerecited in claim 2, further comprising longitudinal ridges and grooveson said smooth outer surface.
 4. The device recited in claim 1, furthercomprising an irregular interior surface within at least one of saidfirst and second elongated segments, said irregular interior surfacebeing adapted to induce mixing within a pressurized said working fluid.5. The device recited in claim 1, further comprising a clot inhibitingouter surface coating on at least one of said first and second elongatedsegments.
 6. The device recited in claim 1, wherein said first andsecond elongated elements are formed from highly conductive material. 7.The device recited in claim 1, further comprising: a coaxial supplycatheter having an inner catheter lumen coupled to said inner lumen ofsaid tubular conduit; and a working fluid supply configured to dispensesaid working fluid and having an output coupled to said inner catheterlumen.
 8. The device recited in claim 7, wherein said working fluidsupply is adapted to dispense a perfluorocarbon working fluid.
 9. Thedevice recited in claim 7, wherein said working fluid supply is adaptedto produce a pressurized said working fluid at a temperature less thanabout 0 degrees C.
 10. The device recited in claim 1, furthercomprising: at least one additional elongated segment; and at least oneadditional bellows connecting said at least one additional elongatedsegment to one of said first and second elongated segments.